WO2021020820A1 - 유데나필을 함유하는 약제학적 조성물 - Google Patents

유데나필을 함유하는 약제학적 조성물 Download PDF

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WO2021020820A1
WO2021020820A1 PCT/KR2020/009800 KR2020009800W WO2021020820A1 WO 2021020820 A1 WO2021020820 A1 WO 2021020820A1 KR 2020009800 W KR2020009800 W KR 2020009800W WO 2021020820 A1 WO2021020820 A1 WO 2021020820A1
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Prior art keywords
pharmaceutical composition
cyclodextrin
acid
fontan
gum
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PCT/KR2020/009800
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English (en)
French (fr)
Korean (ko)
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김상욱
임현태
김영래
김정태
Original Assignee
주식회사 코아팜바이오
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Priority to US17/627,722 priority Critical patent/US20220249493A1/en
Priority to CN202080053706.8A priority patent/CN114173761B/zh
Priority to EP20848224.0A priority patent/EP4005556A4/en
Priority to JP2022505263A priority patent/JP2022542587A/ja
Publication of WO2021020820A1 publication Critical patent/WO2021020820A1/ko

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the present invention relates to a pharmaceutical composition containing udenafil as an active ingredient.
  • Udenafil is 5-[2-propyloxy-5-(1-methyl-2-pyrrolidinyleneamidosulfonyl)phenyl]-1-methyl-1-propyl-1,6-dihydro-7H-pyra
  • a zolo(4,3-d)pyrimidin-7-one compound it is a phosphodiestase type 5 inhibitor, and is a drug currently on the market for the treatment of erectile dysfunction as an indication.
  • the structural formula of udenafil is as follows:
  • Korean Patent Registration Nos. 10-0792126 and 10-0496372 disclose the use of udenafil for the treatment of pulmonary arterial hypertension, portal vein hypertension, and prostatic hyperplasia as a medicinal use of udenafil, and Korean Laid-Open Patent Publication No. 10-2017-0066334 The issue discloses a method of improving myocardial performance in patients with Fontan procedure using a udenafil composition.
  • the Fontan procedure is a palliative surgical procedure for a child born with functional single ventricular congenital heart disease. It began with a procedure that directly connects the right atrium and pulmonary artery when the right ventricle cannot be used. This procedure was conceived from the discovery that unlike the left ventricle, the right ventricle is not necessary to maintain pulmonary artery blood flow.
  • the Fontan procedure is applied to patients with right ventricular dysplasia, tricuspid valve atresia, and single ventricle patients with only one ventricle. In recent years, many surgical methods have been modified, and a technique of connecting to the pulmonary artery directly from the vena cava or using a graft has been used.
  • udenafil which is currently used as a treatment for erectile dysfunction, is commercialized as a tablet formulation, so it is difficult to administer it to patients with dysphagia and infants.
  • Patent Document 1 Korean Patent Registration No. 10-0792126
  • Patent Document 2 Korean Patent Registration No. 10-0496372
  • Patent Document 3 Korean Patent Application Publication No. 10-2017-0066334
  • the inventors of the present invention have completed the present invention by studying to increase the compliance of infants and toddlers by masking bitter taste and numbness when formulating udenafil or a pharmaceutically acceptable salt thereof in a liquid or syrup formulation.
  • an object of the present invention is an oral liquid formulation containing udenafil masking bitter taste or a pharmaceutically acceptable salt thereof (as according to the 11th revision of the Korean Pharmacopoeia, for example, liquid formulations, suspensions, lemonades, etc. Including) or to provide a syrup.
  • the present invention is to provide an oral liquid preparation or syrup containing udenafil or a pharmaceutically acceptable salt thereof, with improved uniformity of the main ingredient.
  • the present invention relates to udenafil or a pharmaceutically vanity salt thereof; pH adjuster; And a pharmaceutical composition comprising cyclodextrin or a derivative thereof.
  • composition of the present invention is intended to be administered to patients undergoing Fontan, and is preferably a liquid formulation or a syrup formulation to facilitate oral administration by infants and young children.
  • the composition of the present invention may further include a viscosity modifier.
  • the viscosity is preferably 400 ⁇ 4000 cps.
  • the pH of the composition of the present invention is preferably in the range of 3 to 6.
  • the cyclodextrin derivatives are ⁇ -cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin, 2-hydroxypropyl ⁇ -cyclodextrin, 2,6-dimethyl- ⁇ -cyclodextrin, sulfobutylether-7- ⁇ -cyclodextrin, 2-hydroxyethyl- ⁇ -cyclodextrin, (2-carboxymethoxy)propyl- ⁇ -cyclodextrin, 2-hydroxyethyl- ⁇ -cyclodextrin and 2-hydroxypropyl- ⁇ -cyclo
  • One or more types may be selected and used from the group consisting of dextrin.
  • the weight ratio of the udenafil or a pharmaceutically acceptable salt thereof and the cyclodextrin or a derivative thereof is preferably 1:0.1 to 10.
  • the viscosity modifier is agar, xanthan gum, locust bean gum, guar gum, tragacanth gum, gum arabic, gellan gum, karaya gum, gati gum, tamarind gum, tara gum, acacia gum, chitosan, carrageenan, gelatin , Pectin, alginic acid, sodium alginate, propylene glycol, hypromellose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose, polyethylene glycol, polyvinyl alcohol, povidone and at least one kind from the group consisting of polyethylene oxide Can be chosen.
  • the pH adjusting agent may be selected from one or more of the group consisting of citric acid, fumaric acid, succinic acid, adipic acid, aspartic acid, glutamic acid, maleic acid, lactic acid, tartaric acid, phosphoric acid, hydrochloric acid, acetic acid, and the like.
  • the pharmaceutical composition containing udenafil or a pharmaceutically acceptable salt thereof according to the present invention minimizes the inherent bitter taste and numbness of the drug, thereby improving adherence to the medication of infants and infants and patients with dysphagia.
  • the uniformity of the liquid or syrup is secured, layer separation does not occur, and flowability is good, so that a liquid or syrup composition containing udenafil of excellent quality can be provided.
  • the present invention relates to udenafil or a pharmaceutically vanity salt thereof; pH adjuster; And a pharmaceutical composition comprising cyclodextrin or a derivative thereof.
  • the term "pharmaceutically acceptable salt” means a salt commonly used in the pharmaceutical industry, for example, inorganic ion salts prepared from calcium, potassium, sodium, magnesium, hydrochloric acid, nitric acid, Inorganic acid salts prepared from phosphoric acid, bromic acid, iodic acid, perchloric acid and sulfuric acid; Acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, manderic acid, propionic acid, lactic acid, glycolic acid, gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid Organic acid salts prepared from acids, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, and the like; Sulfonic acid salts prepared from methanesulfonic acid, ethanesulfonic acid, benzenesul
  • the composition of the present invention relates to a pharmaceutical composition for administration to a patient undergoing Fontan treatment, and by treating or preventing conditions, symptoms and/or side effects associated with patients undergoing Fontan treatment, for example, improving cardiac output or It can reduce vascular resistance, increase exercise capacity, improve myocardial performance, or improve aerobic exercise performance.
  • composition of the present invention relates to a pharmaceutical composition for preventing or treating erectile dysfunction, and improves adherence to medication of patients with erectile dysfunction (particularly, patients with difficulty swallowing).
  • prevention means a delay in onset of a disease, disorder or disease. Prevention can be considered complete if the onset of the disease, disorder or condition is delayed for a predetermined period of time.
  • treatment'' partially or completely reduces, ameliorates, alleviates, inhibits or delays the onset of a specific disease, disorder, and/or disease, reduces the severity, or generates one or more symptoms or characteristics. Means to reduce.
  • the pharmaceutical composition of the present invention is formulated using a pharmaceutically acceptable carrier according to a method that can be easily carried out by a person skilled in the art to which the present invention belongs. It can be manufactured in unit dosage form or can be manufactured by putting it inside a multi-dose container.
  • the term “carrier” means a compound that facilitates the addition of the compound into cells or tissues
  • pharmaceutically acceptable is physiologically acceptable and when administered to humans, it is usually It refers to a composition that does not cause allergic reactions or similar reactions such as gastrointestinal disorders and dizziness.
  • the pharmaceutically acceptable carrier is commonly used at the time of formulation, and lactose, dextrose, sucrose, sorbitol, mannitol, starch, gum acacia, calcium phosphate, alginate, gelatin , Calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup, methyl cellulose, methyl hydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, mineral oil, etc. It is not limited.
  • the pharmaceutical composition of the present invention may further include a lubricant, a wetting agent, a sweetening agent, a flavoring agent, an emulsifying agent, a suspending agent, a preservative, and the like in addition to the above components.
  • the content of the additive included in the pharmaceutical composition is not particularly limited and may be appropriately adjusted within the content range used for conventional formulation.
  • composition of the present invention is preferably a liquid formulation or a syrup formulation to facilitate oral administration by infants and toddlers who have undergone the Fontan procedure according to the intended administration mode.
  • the term ⁇ administration'' refers to providing a predetermined substance to an individual or patient by any appropriate method, and parenteral administration (for example, intravenous, subcutaneous, intraperitoneal or Topically applied as an injection formulation) or oral administration, and the dosage range varies depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease.
  • parenteral administration for example, intravenous, subcutaneous, intraperitoneal or Topically applied as an injection formulation
  • oral administration for example, intravenous, subcutaneous, intraperitoneal or Topically applied as an injection formulation
  • the dosage range varies depending on the patient's weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of disease.
  • the composition of the present invention is preferably administered orally.
  • oral administration means that the active substance is administered to the gastrointestinal tract for absorption.
  • a binder such as lactose, saccharose, sorbitol, mannitol, starch, amylopectin, cellulose or gelatin; Excipients such as dicalcium phosphate and the like; Disintegrants such as corn starch or sweet potato starch; Lubricating oils such as magnesium stearate, calcium stearate, sodium stearyl fumarate or polyethylene glycol may be used, and sweeteners, fragrances, syrups, and the like may also be used.
  • a liquid carrier such as fatty oil may be additionally used.
  • the preferred dosage of the pharmaceutical composition of the present invention is the patient's condition and weight, age, sex, health condition, dietary constitution specificity, nature of the formulation, degree of disease, administration time of the composition, administration method, administration period or interval, excretion
  • the range may vary depending on the rate and the drug type, and may be appropriately selected by a person skilled in the art. For example, it may be in the range of about 0.1 to 10,000 mg/kg, but is not limited thereto, and may be administered in divided doses from once to several times a day.
  • the pharmaceutical composition of the present invention may include two separate agents, may be composed of one agent, but is not limited thereto.
  • liquid preparation means a drug taken in the form of a drug dissolved in water or an organic solvent.
  • the liquid formulation has the advantage of more effective absorption of the drug into the systemic circulation in the intestine than the suspension or solid formulation, and the liquid formulation may contain additional solutes in addition to the drug, and gives color, odor, sweetness or stability. Additives may also be included.
  • the term "syrup agent” means a concentrated handmade sugar or sugar substitute.
  • the syrup is a pharmaceutical product having an unpleasant taste, such as a bitter taste, which is easily taken as a liquid, and is a formulation suitable for children to take.
  • the syrup agent in the present invention may include, in addition to purified water and extracts, sugar or sugar substitutes used to give sweetness and viscosity, antibacterial preservatives, flavors, or coloring agents, but are not limited thereto.
  • sweeteners examples include sucrose, mannitol, sorbitol, xylitol, aspartame, stevioside, fructose, lactose, sucralose, saccharin, or menthol, but are not limited thereto.
  • the composition of the present invention may further include a viscosity modifier.
  • the viscosity is preferably 400 ⁇ 4000 cps, but is not limited thereto.
  • the pH of the composition of the present invention is preferably in the range of 3 to 6, but is not limited thereto.
  • centipoise means a centipoise which is a unit of viscosity.
  • cyclodextrin derivative refers to a compound or a part of a compound that can be derived from cyclodextrin.
  • the cyclodextrin derivatives include ⁇ -cyclodextrin, ⁇ -cyclodextrin, ⁇ -cyclodextrin, 2-hydroxypropyl- ⁇ -cyclodextrin, 2,6-dimethyl- ⁇ -cyclodextrin, sulfobutylether- 7- ⁇ -cyclodextrin, 2-hydroxyethyl- ⁇ -cyclodextrin, (2-carboxymethoxy)propyl- ⁇ -cyclodextrin, 2-hydroxyethyl- ⁇ -cyclodextrin and 2-hydroxypropyl- ⁇ -One or more selected from the group consisting of cyclodextrin may be used, and specifically, it is preferable to use ⁇ -cyclodextrin alone or in combination of ⁇ -cyclodextrin and ⁇ -cyclodextrin.
  • the weight ratio of the udenafil or a pharmaceutically acceptable salt thereof and the cyclodextrin or a derivative thereof is preferably 1:0.1 to 10, and more specifically, udenafil or a pharmaceutically acceptable salt thereof and It is more preferable that the weight ratio of the cyclodextrin or a derivative thereof is 1:1 to 5.
  • viscosity control agent refers to a substance used to maintain a stable state without layer separation by combining a liquid phase and a solid phase in a pharmaceutical composition, and to increase the viscosity of the pharmaceutical composition.
  • the viscosity modifier is agar, xanthan gum, locust bean gum, guar gum, tragacanth gum, gum arabic, gellan gum, karaya gum, gati gum, tamarind gum, tara gum, acacia gum, chitosan, carrageenan, gelatin , Pectin, alginic acid, sodium alginate, propylene glycol, hypromellose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methyl cellulose, polyethylene glycol, polyvinyl alcohol, povidone and at least one kind from the group consisting of polyethylene oxide May be selected, but is not limited thereto.
  • pH adjusting agent means an excipient used to adjust the pH of a pharmaceutical composition to a desired value.
  • the pH adjusting agent may be one or more selected from the group consisting of citric acid, fumaric acid, succinic acid, adipic acid, aspartic acid, glutamic acid, maleic acid, lactic acid, tartaric acid, phosphoric acid, hydrochloric acid, acetic acid, and the like. It is not limited.
  • the present invention provides a method for preventing or treating Fontan disease and pulmonary hypertension or erectile dysfunction associated with Fontan disease and comprising administering the pharmaceutical composition in a therapeutically effective amount to mammals, including humans. .
  • the term "therapeutically effective amount” means a pharmaceutical composition administered to a subject to be treated in an amount effective for the prevention or treatment of pulmonary hypertension or erectile dysfunction associated with Fontan disease and Fontan disease.
  • an amount of Fontan disease and preventing the occurrence or recurrence of pulmonary hypertension or erectile dysfunction associated with Fontan disease alleviating symptoms, inhibiting direct or indirect pathological consequences, preventing metastasis, or Any amount of the pharmaceutical composition that reduces the rate of progression, alleviates or temporarily alleviates the condition, or improves the prognosis may be included. That is, the therapeutically effective amount may be interpreted as encompassing all doses for improving or curing symptoms of Fontan disease and pulmonary hypertension or erectile dysfunction associated with Fontan disease and Fontan disease by the pharmaceutical composition.
  • the Fontan disease and a method for preventing or treating pulmonary hypertension or erectile dysfunction related to Fontan disease, by administering the pharmaceutical composition not only treats the disease itself before the onset of the symptoms, but also inhibits or avoids the symptoms thereof. Also includes.
  • the prophylactic or therapeutic dose of a particular active ingredient will vary depending on the nature and severity of the disease or condition and the route to which the active ingredient is administered. The dose and frequency of dose will vary depending on the age, weight and response of the individual patient. A suitable dosage regimen can be readily selected by one of ordinary skill in the art taking these factors of course into account.
  • the prophylaxis or treatment method of the present invention comprises administration of a therapeutically effective amount of an additional active agent useful in the prevention or treatment of Fontan disease and pulmonary hypertension or erectile dysfunction associated with Fontan disease and Fontan disease together with the pharmaceutical composition. It may further include, and the additional active agent may exhibit a synergistic effect or an additive effect with the pharmaceutical composition.
  • mamal including human includes mammals such as humans, monkeys, cows, horses, dogs, cats, rabbits, and rats.
  • the present invention provides the use of the pharmaceutical composition for use in the manufacture of pulmonary hypertension or erectile dysfunction agents associated with Fontan disease and Fontan disease.
  • the present invention provides the use of the pharmaceutical composition for the treatment of Fontan disease and pulmonary hypertension or erectile dysfunction associated with Fontan disease.
  • the pharmaceutical composition of the present invention for the manufacture of a formulation for pulmonary hypertension or erectile dysfunction related to Fontan disease and Fontan disease may contain an acceptable carrier, etc., and may further include other agents.
  • a pH adjuster was added to 5 ml of purified water, stirred for 10 minutes, and then udenafil was added to prepare as shown in Table 1. After stirring each solution for 2 hours, a sample was taken and filtered with a 0.45 ⁇ m PVDF syringe filter to perform a solubility test, and the pH was measured (pH measuring instrument: pH2700, EUTECH, USA.).
  • UV detector (292 nm)
  • the water solubility of udenafil is about 0.12mg/mL (Comparative Example 1), which has extremely poorly soluble physical properties, and in the above test, it was confirmed that the solubility of udenafil changes according to the pH of the solution. It was seen that the solubility was improved in Preparation Example 1 having a pH of 6.83, and the solubility was greatly increased in Preparation Example 4 (pH 6.1) having a low pH. However, in Preparation Examples 7 and 8 where the pH was lower than 2, the solubility was partially reduced than the range of pH 3 to 6.
  • udenafil has the highest solubility in the range of pH 3-6.
  • a composition in which udenafil was added to purified water in the composition and content of Table 3 (Comparative Example 1) and a composition in which udenafil was completely dissolved (Comparative Example 2) by adjusting the pH with a pH adjuster were prepared, respectively.
  • Comparative Example 1 Prepared by adding udenafil to 100 ml of purified water and stirring for 20 minutes.
  • Comparative Example 2 A pH adjuster was added to 100 ml of purified water and stirred for 10 minutes, and udenafil was added to this solution, followed by stirring for 20 minutes.
  • Udenafil syrup compositions that do not contain cyclodextrin were prepared in the compositions shown in Table 4 below. Since the composition of Comparative Example 3 does not contain a pH adjusting agent, udenafil is not completely dissolved.
  • a pH adjuster is added to 20 ml of purified water and stirred for 10 minutes (however, this step is omitted when preparing Comparative Example 3 in which a pH adjuster is not used).
  • step (iv) The solution prepared in step (ii) is mixed with the solution prepared in step (iii), stirred, cooled, and then added to purified water to mark 100 ml to prepare a composition.
  • Udenafil syrup compositions containing cyclodextrin were prepared in the compositions of Tables 5-1 and 5-2, respectively. Since the composition of Comparative Example 5 does not contain a pH adjusting agent, udenafil is not completely dissolved.
  • a pH adjuster is added to 20 ml of purified water and stirred for 10 minutes (however, this step is omitted when preparing Comparative Example 5 in which a pH adjuster is not used).
  • step (v) The solution prepared in step (iii) is mixed with the solution prepared in step (iv), stirred, cooled, and then added to purified water to mark 100 ml to prepare a composition.
  • a udenafil syrup composition containing cyclodextrin and a viscosity modifier was prepared in the composition of Table 6 below.
  • step (v) The solution prepared in step (iii) is mixed with the solution prepared in step (iv), stirred, cooled, and then added to purified water to mark 100 ml to prepare a composition.
  • Udenafil syrup compositions were prepared with the compositions of Tables 7-1, 7-2, and 7-3 below.
  • step (v) The solution prepared in step (iii) is mixed with the solution prepared in step (iv), stirred, cooled, and then added to purified water to mark 100 ml to prepare a composition.
  • Comparative Examples 5 and 6 used ⁇ -cyclodextrin, but due to the udenafil particles that were not completely dissolved and dispersed, the evaluation values of bitter taste and numbness were not significantly different from those of Comparative Examples 2 and 3.
  • composition of the other Comparative Examples and Examples was found to decrease bitter taste and numbness as cyclodextrin was added, and in particular, it was confirmed that numbness was significantly reduced.
  • the pH of the composition is most suitable in the range of pH 3-6, which is the range in which the solubility of udenafil is the highest.
  • compositions of Examples 1 to 20 suitable for this criterion showed satisfactory results in all items of layer separation, flowability, bitter taste, and numbness when compared with the compositions of Comparative Examples 1 to 23.
  • Example 6 which showed all suitable results from the above results, was selected, and properties (layer separation), content, related substances, under severe conditions (60°C) and accelerated conditions (40°C, 75%RH) to confirm stability
  • the pH and viscosity were evaluated.
  • the test results are shown in Table 14 and Fig. 1 below.
  • UV detector (292 nm)
  • composition of the Example showed suitable results in all items of properties, content, related substances, pH, and viscosity.
  • the pharmaceutical composition containing udenafil or a pharmaceutically acceptable salt thereof according to the present invention minimizes the inherent bitter taste and numbness of the drug, thereby improving the medication compliance of infants and toddlers who are the main targets.

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PCT/KR2020/009800 2019-07-26 2020-07-24 유데나필을 함유하는 약제학적 조성물 WO2021020820A1 (ko)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US17/627,722 US20220249493A1 (en) 2019-07-26 2020-07-24 Pharmaceutical composition comprising udenafil
CN202080053706.8A CN114173761B (zh) 2019-07-26 2020-07-24 包含乌地那非的药物组合物
EP20848224.0A EP4005556A4 (en) 2019-07-26 2020-07-24 PHARMACEUTICAL COMPOSITION CONTAINING UDENAFIL
JP2022505263A JP2022542587A (ja) 2019-07-26 2020-07-24 ウデナフィルを含む薬学的組成物

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KR10-2019-0091056 2019-07-26
KR1020190091056A KR102249155B1 (ko) 2019-07-26 2019-07-26 유데나필을 함유하는 약제학적 조성물

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KR20240045074A (ko) * 2022-09-29 2024-04-05 주식회사태준제약 브리모니딘을 포함하는 안과용 조성물

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20030042547A (ko) * 2001-11-23 2003-06-02 주식회사 에이치팜 레보설피리드 액제 조성물 및 그의 제조방법
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KR20210012760A (ko) 2021-02-03
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